RT Journal
A1 Zimmerman, Stephanie M.
A1 Fropf, Robin
A1 Kulasekara, Bridget R.
A1 Griswold, Maddy
A1 Appelbe, Oliver
A1 Bahrami, Arya
A1 Boykin, Rich
A1 Buhr, Derek L.
A1 Fuhrman, Kit
A1 Hoang, Margaret L.
A1 Huynh, Quoc
A1 Isgur, Lesley
A1 Klock, Andrew
A1 Kutchma, Alecksandr
A1 Lasley, Alexa E.
A1 Liang, Yan
A1 McKay-Fleisch, Jill
A1 Nelson, Jeffrey S.
A1 Nguyen, Karen
A1 Piazza, Erin
A1 Rininger, Aric
A1 Zollinger, Daniel R.
A1 Rhodes, Michael
A1 Beechem, Joseph M.
T1 Spatially resolved whole transcriptome profiling in human and mouse tissue using Digital Spatial Profiling
JF Genome Research 
JO Genome Research 
YR 2022 
FD October 01 
VO 32 
IS 10 
SP 1892 
OP 1905 
DO 10.1101/gr.276206.121 
UL http://genome.cshlp.org/content/32/10/1892.abstract 
AB Emerging spatial profiling technology has enabled high-plex molecular profiling in biological tissues, preserving the spatial and morphological context of gene expression. Here, we describe expanding the chemistry for the Digital Spatial Profiling platform to quantify whole transcriptomes in human and mouse tissues using a wide range of spatial profiling strategies and sample types. We designed multiplexed in situ hybridization probes targeting the protein-coding genes of the human and mouse transcriptomes, referred to as the human or mouse Whole Transcriptome Atlas (WTA). Human and mouse WTAs were validated in cell lines for concordance with orthogonal gene expression profiling methods in regions ranging from ∼10–500 cells. By benchmarking against bulk RNA-seq and fluorescence in situ hybridization, we show robust transcript detection down to ∼100 transcripts per region. To assess the performance of WTA across tissue and sample types, we applied WTA to biological questions in cancer, molecular pathology, and developmental biology. Spatial profiling with WTA detected expected gene expression differences between tumor and tumor microenvironment, identified disease-specific gene expression heterogeneity in histological structures of the human kidney, and comprehensively mapped transcriptional programs in anatomical substructures of nine organs in the developing mouse embryo. Digital Spatial Profiling technology with the WTA assays provides a flexible method for spatial whole transcriptome profiling applicable to diverse tissue types and biological contexts.